DOI: 10.14260/jemds/2014/1991
ORIGINAL ARTICLE
SERUM TOTAL CALCIUM, SERUM IONIZED CALCIUM AND SERUM ALBUMIN
LEVELS IN PATIENTS WITH ESSENTIAL HYPERTENSION AND THEIR FIRST
DEGREE RELATIVES
Arpita B. Patel1, N. Haridas2, Hitesh Shah3
HOW TO CITE THIS ARTICLE:
Arpita B. Patel, N. Haridas, Hitesh Shah. “Serum Total Calcium, Serum Ionized Calcium and Serum Albumin
Levels in patients with Essential Hypertension and their First Degree Relatives”. Journal of Evolution of Medical
and Dental Sciences 2014; Vol. 3, Issue 06, February 10; Page: 1354-1360, DOI: 10.14260/jemds/2014/1991
ABSTRACT: Calcium plays an important role in pathophysiology of essential hypertension. (1) Serum
total calcium, serum ionized calcium and serum albumin levels were measured in 50 subjects with
essential hypertension and 50 first degree relatives with familial history of hypertension. The same
were also measured in 50 normotensive subjects and 50 first degree relatives having no familial
history of hypertension. The results showed that serum total calcium and serum albumin levels were
significantly decreased in both males and females with essential hypertension and their first degree
relatives when compared with their corresponding controls. While serum ionized calcium levels were
not significantly different in hypertensives and their first degree relatives.
KEYWORDS: Essential hypertension, First degree relatives, controls.
INTRODUCTION: Hypertension is a cardiac chronic medical condition in which the systemic arterial
blood pressure is elevated. 1Hypertension is classified as either primary or secondary. About 90 –
95% of causes are categorized as primary hypertension which means high blood pressure with no
obvious medical cause.2 The remaining 5 -10% cases are caused by other conditions that affect the
kidneys, arteries, heart or endocrine system.3 Essential hypertension is the most prevalent
hypertension type, affecting 90–95% of hypertensive patients. Essential hypertension is associated
with disturbed calcium metabolism. The calcium ions play a major role as a second messenger in
excitation contraction coupling in cardiac and smooth muscle cells.4
Low serum albumin concentrations appear to be associated with an increased risk of
coronary diseases in both sexes and could help along with traditional risk factors in identifying
people at risk of myocardial infarction.5
As the results reported by various authors on serum total calcium1, 6, 7 and serum albumin8
were found to be varying, it was planned to study serum total calcium, serum ionized calcium and
serum albumin levels in patients with essential hypertension, their first degree relatives and in
normal controls.
MATERIALS AND METHODS: The blood samples were collected from 50 hypertensives, 50 first
degree relatives with familial history of hypertension, 50 normotensive subjects and 50 first degree
relatives having no familial history of hypertension. The subjects included both males and females.
The blood was collected in plain vacutte by venepuncture. The samples were centrifuged and serum
was used for measurements.
Serum total calcium estimation was done on an automated analyzer, COBAS INTEGRA 400
Plus. Method is according to Schwarzenbach with O- cresolphthelein (O- CPC) complex one. Calcium
Journal of Evolution of Medical and Dental Sciences/ Volume 3/ Issue 06/February 10, 2014
Page 1354
DOI: 10.14260/jemds/2014/1991
ORIGINAL ARTICLE
ions react with O- cresolphthelein under alkaline conditions to form a violet colored complex. The
addition of 8- hydroxyl quinoline prevents interference by Magnesium and ferric ions. 9
The color intensity of the complex formed is directly proportional to the calcium
concentration. It is determined by measuring the increase in absorbance at 552 nm. The value is
expressed in mg / dl. 9
Serum ionized calcium measurement was done on AVL 9180 Electrolyte Analyzer. The AVL
9180 Electrolyte Analyzer methodology is based on the ion selective electrode measurement
principle to precisely determine the measurement value.10
The serum albumin estimation was done by colorimetric method on RA 50 Chemistry
Analyzer. The test procedure is followed by manufacturer’s instructions and absorbance is taken as
optical density. 11
Albumin in a buffered solution reacts with the anionic bromocresol green (BCG) with a dye
binding reaction to give a proportionate green color, which is measured at 620nm.The final color is
stable for 10 minutes. 11
The concentration of Albumin in a sample from absorbance is calculated by the following
formula:
OD of Test
Concentration of Test =
× Concentration of Standard
OD of Standard
The value is expressed in g/dl.
RESULTS: The results of the study are depicted in tables 1 and 2. The serum total calcium, serum
ionized calcium and serum albumin levels in hypertensives and their first degree relatives and
normotensives and their first degree relatives are shown in table no.1.
Tests
Total calcium
(mg/dl)
Ionized
calcium(mmol/L)
Albumin
(g/dl)
95% C.I. for
Hypertensives
95% C.I. for
Controls of
normotensives
N
Mean ± SD
N
Mean ± SD
95% C.I. for First
degree relatives
(FDR) of
hypertensives
N
Mean ± SD
50
8.35 ± 0.63
50
9.53 ± 0.51
50
50
1.11 ± 0.11
50
1.14 ± 0.085
50
4.07 ± 0.75
50
4.61 ± 0.45
95% C.I. for
Controls (FDR) of
normotensives
N
Mean ± SD
8.81 ± 0.59
50
9.33 ± 0.45
50
1.14 ± 0.089
50
1.15 ± 0.083
50
4.35 ± 0.64
50
4.61 ± 0.39
TABLE NO.1: Serum total calcium, serum ionized calcium and serum albumin levels in hypertensives
and their first degree relatives and normotensives and their first degree relatives
C.I. = confidence interval
Journal of Evolution of Medical and Dental Sciences/ Volume 3/ Issue 06/February 10, 2014
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DOI: 10.14260/jemds/2014/1991
ORIGINAL ARTICLE
Parameter
Total calcium
(mg/dl )
Ionized calcium
(mmol/L)
Albumin (g/dl)
FDR
Total calcium
(mg/dl)
FDR
Ionized
calcium(mmol/L)
FDR
Albumin (g/dl)
Category
N = 50
Mean± SD
Hypertensives 8.35 ± 0.63
Normotensives 9.53±0.51
Hypertensives 1.11±0.11
Normotensives 1.14±0.085
Hypertensives 4.07±0.75
Normotensives 4.61±0.45
Hypertensives 8.81±0.59
Normotensives
Mean
difference
P Value
-1.179
<0.0001
-0.035
0.088
-0.07
0.01
-0.544
<0.0001
-0.79
-0.29
-0.520
<0.0001
-0.73
-0.31
-0.04
0.020
-0.48
-0.05
9.33±0.45
1.14
-0.008
0.629
±0.089
Normotensives 1.15±0.083
Hypertensives 4.35±0.64
-0.266
0.014
Normotensives 4.61 ±0.39
TABLE NO.2: Independent samples test (t- TEST)
Hypertensives
95% confidence
interval of the
difference
Lower
upper
-1.40
-0.95
<0.05 = significant difference



When serum total calcium levels of hypertensives and normotensives were compared, the P
value mean total calcium level of normotensives had statistically significant higher values
than the mean total calcium levels of hypertensives.
When serum albumin levels of hypertensives and normotensives were compared, the mean
albumin level of normotensives had statistically significant higher values than the mean
albumin levels of hypertensives.
When serum ionized calcium levels of hypertensives and normotensives were compared, the
mean ionized calcium level of normotensives had slightly higher values. But there was no
statistically significant difference between mean ionized calcium levels of hypertensive and
normotensive groups.
The mean ± SD of serum total calcium levels in normotensives were 9.53 ± 0.51 and the same
was found to be decreased in hypertensive groups (8.35 ± 0.63). We found that there was statistically
significant difference between mean total calcium levels in males of hypertensives and
normotensives category. We also found that there was statistically significant difference between
mean total calcium levels in females of hypertensives and normotensives category. When the first
degree relatives were considered, the first degree relatives of hypertensives had statistically
significant lower mean± SD serum total calcium levels (8.81 ±0.59), when compared to the first
degree relatives of normotensive (9.33 ±0.45). P value is <0.05.
Journal of Evolution of Medical and Dental Sciences/ Volume 3/ Issue 06/February 10, 2014
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DOI: 10.14260/jemds/2014/1991
ORIGINAL ARTICLE
The mean ± SD serum albumin levels in normotensives were 4.61 ± 0.39 and the same was
decreased for hypertensive groups (4.07 ± 075). We found that there was statistically significant
difference between mean albumin levels in males of hypertensives and normotensives category. We
also found that there was statistically significant difference between mean albumin levels in females
of hypertensives and normotensives category. When the first degree relatives were considered, the
first degree relatives of hypertensives had statistically significant lower mean ± SD serum albumin
levels (4.35 ±0.64), when compared to the first degree relatives of normotensives (4.61 ±0.39). P
value is < 0.05.
The mean ± SD serum ionized calcium levels in normotensives were 1.14 ±0.085 and the
same were comparable without any statistically significant difference in hypertensive groups (1.11
±0.11). We found that there was no statistically significant difference between mean ionized calcium
levels in males of hypertensives and normotensives category. We also found that there was no
statistically significant difference between mean ionized calcium levels in females of hypertensives
and normotensives category. When the first degree relatives were considered, the first degree
relatives of hypertensives had slightly lower mean ± SD ionized calcium level (1.14 ±0.089), but there
was no statistically significant difference when compared to the first degree relatives of
normotensives (1.15 ±0.083), P value is >0.05.
DISCUSSION: Essential hypertension is associated with disturbed calcium metabolism. Individuals
with high diastolic blood pressure had significantly lower total serum calcium. 6 The free intracellular
calcium concentration determines the tension in vascular smooth muscle cells thereby resulting in
peripheral vascular resistance.1 Zidek et al found an increased intravascular calcium concentration in
normotensive subjects with familial hypertensive disposition in comparison with Normotensives
without family history of hypertension.12
Touyz et al showed significantly increased intracellular calcium levels in essential
hypertension.13 Some authors have reported lower concentration of serum calcium in hypertensive
than in normotensive subjects.14, 15
The present study shows significantly reduced serum total calcium and albumin levels in
hypertensives. While the serum ionized calcium levels are comparable in both groups as there is no
significant difference. This is in agreements with studies of K. Sudhakar et al1 and Reichel et al. 6
Serum calcium levels were also found to be significantly lower by Fu. Y., Wang et al14 and
Touyz. R. M. et al.16 Reichel et al also reported reduced calcium level in males with elevated diastolic
blood pressure.6 Kosch et al did not find any change in serum calcium levels in hypertensives when
compared to controls. Membrane calcium content was significantly increased in patients with
untreated primary hypertension and correlated to blood pressure levels in their studies. The data
suggested that membrane mechanism may contribute to alterations in calcium metabolism and to the
pathogenesis of primary hypertension. 7
Abnormal cellular ion transport resulting in altered membrane control over intracellular
calcium may be related to essential hypertension. Changes in magnesium level may contribute to
altered cell membrane, calcium binding in essential hypertension. 17Alterations in intracellular
calcium are thought to be involved in the common pathway mediating the secretion and action of
many hormones including the pressure action of catecholamines and Angiotensin II. Intracellular
calcium may be involved in regulation of blood pressure. Calcium regulating hormones like 1, 25Journal of Evolution of Medical and Dental Sciences/ Volume 3/ Issue 06/February 10, 2014
Page 1357
DOI: 10.14260/jemds/2014/1991
ORIGINAL ARTICLE
Dihydroxy vitamin D levels of plasma, renin activity, and circulating ionized calcium contribute to the
pathophysiology of the essential hypertension. 18, 19
Yogesh R Pawade et al studied at Nagpur, had found that Serum total calcium was found to be
same in the hypertensive as well as the normotensive population but serum ionized calcium was
observed to be decreased in the hypertensive subjects as compared to the normotensive subjects.
Decreased levels of serum ionized calcium are associated with essential hypertension. 20 But in our
study, the serum ionized calcium levels in normotensives and hypertensives were not significantly
different. However, this author has not studied on serum albumin levels. These results are not
matching with my study.
Albumin has low affinity and high capacity binding potential for most of the molecules that
may be the actual unmeasured substances regulating blood pressure. Serum albumin has been
demonstrated to have a blood pressure lowering effect in animal studies. Serum albumin is also
associated with systolic blood pressure and diastolic blood pressure. 8
CONCLUSION:
(1) The serum total calcium levels are found to be lower in hypertensive males and females in
comparison to the corresponding controls. The serum total calcium levels are also found to be
lower in the first degree relatives of the hypertensives when compared with the
corresponding controls. The data correlates well with the other previous studies.
(2) The study shows that there is no significant difference in serum ionized calcium levels of
hypertensives when compared to the corresponding controls. The levels are also comparable
in the first degree relatives of hypertensives and corresponding controls.
(3) Our study shows that there is significant decrease in serum albumin levels in hypertensives
and their first degree relatives when compared with the corresponding controls.
(4) The present study shows there may be a role of serum total calcium in the pathophysiology of
hypertension, although, further studies are required to confirm these observations.
(5) Serum total calcium and serum albumin estimation may be used to predict the risk of
hypertension in normotensives with familial history of hypertension.
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2000; 101(3):329-35.
3. Secondary Hypertension, Mayo foundation for medical education and research (2008) [1],
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4. K. Sudhakar, M. Sujatha, S. Rameshbabu, P. Padmavathi and P.P Reddy. Serum calcium levels in
patients with essential hypertension and their first degree relatives. Ind J of clinical
Biochemistry, 2004, 19(1) 21-23.
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(21): 222-223, D(28): 300-303.
6. Reichel H, Leibethal R., Hense, H.W., Schmidt, G.H., and Ritz, E. Disturbed calcium metabolism in
subjects with elevated diastolic blood pressure. Clin. Investing. 1992: 70, 748-751.
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ORIGINAL ARTICLE
7. Kosch M., Hausberg M., Barembrock M., Posadzy-malaczynskas A., Rahn KH, Kisters K. Increased
membranous calcium concentrations in primary hypertension: a causal link to pathogenesis. J.
Hum. Hypertens. 2001:15,37-40.
8. Howard Hu, David Sparrow and Scott Weiss. Association of serum albumin with blood pressure
in the normative aging study. American Journal of Epidemiology, 1992; 136 (12), 1465-1473.
9. COBAS Integra 400 plus Method’s Manual. A -1 (4-12).
10. AVL 9180 Electrolyte analyzer operator’s manual.
11. RA 50 Chemistry Analyzer Operating Manual; 1 (1.2), 6 (6.1).
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essential hypertension. Clinical Science. 1982; 63, 41S-43S.
13. Touyz R. M. and Milne F.J. Alterations in intracellular cations and cell membrane ATPase activity
in patients with malignant hypertension. J. Hypertens., 1995; 13,867-874.
14. Fu Y., Wang S., Lu Z., Li H. and Li S. Erythrocyte and plasma Ca++, Mg++ and cell membrane
adenosine triphosphatase activity in patients with essential hypertension. Clin. Med. J. (Engl),
1998; 111, 147-149.
15. Touyz R. M., Milne F.J. and Reinach S. G. Intracellular Mg2+, Ca2+, Na+ and K+ in platelets and
erythrocytes of essential hypertension patients: relation to blood pressure. J. Hypertens., 1992;
14, 1189-1209.
16. R. M. Touyz, F. J. Milne, H. C. Seftel, S. G. Reinach. Magnesium, calcium, sodium and potassium
status in normotensive and hypertensive Johannesburg residents. SAMT, 9/1987, vol. 72; 377381.
17. Arvo Haenni, Richard Reneland, Lars Lind and Hans Lithell. Serum aldosterone changes during
hyperinsulinemia are correlated to body mass index and insulin sensitivity in patients with
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18. Resnick L.M. The effects of sodium and calcium in clinical hypertension: mediating role of
Vitamin D metabolism.Adv. Second Messenger Phosphoprotein Res., 1990; 24,535-541.
19. Chlumsky J. Calcium and hypertension. J. Hypertens., 1993; 39, 1181-1184.
20. Yogesh R. Pawade, Suresh S. Ghangale, Indrayani C. Apte, Abhay N. Nagleote, Jayesh P. Warade.
Serum calcium: Can it be a diagnostic and prognostic marker in essential hypertension. JCDR,
original article/ research, 2011; 5 (1), 58-62.
Journal of Evolution of Medical and Dental Sciences/ Volume 3/ Issue 06/February 10, 2014
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DOI: 10.14260/jemds/2014/1991
ORIGINAL ARTICLE
AUTHORS:
1. Arpita B. Patel
2. N. Haridas
3. Hitesh Shah
PARTICULARS OF CONTRIBUTORS:
1. M.Sc. Student, Department of Biochemistry,
Pramukhswami Medical College, Karamsad.
2. Professor and Head, Department of
Biochemistry,
Pramukhswami
Medical
College, Karamsad.
3. Professor, Department of Biochemistry,
Pramukhswami Medical College, Karamsad.
NAME ADDRESS EMAIL ID OF THE
CORRESPONDING AUTHOR:
Arpita B. Patel,
Near Darwaja, Barot Faliya, Lingda,
Ta – Umreth Di – Anand,
Gujarat – 388220.
E-mail: arpee_2008p@yahoo.co.in
Date of Submission: 20/04/2013.
Date of Peer Review: 22/04/2013.
Date of Acceptance: 07/05/2013.
Date of Publishing: 04/02/2014.
Journal of Evolution of Medical and Dental Sciences/ Volume 3/ Issue 06/February 10, 2014
Page 1360